Excitatory neuron-prone prion propagation and excitatory neuronal loss in prion-infected mice

The accumulation of a disease-specific isoform of prion protein (PrP ) and histopathological lesions, such as neuronal loss, are unevenly distributed in the brains of humans and animals affected with prion diseases. This distribution varies depending on the diseases and/or the combinations of prion...

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Veröffentlicht in:Frontiers in molecular neuroscience 2024-12, Vol.17, p.1498142
Hauptverfasser: Erdenebat, Temuulen, Komatsu, Yusuke, Uwamori, Nozomi, Tanaka, Misaki, Hoshika, Takashi, Yamasaki, Takeshi, Shimakura, Ayano, Suzuki, Akio, Sato, Toyotaka, Horiuchi, Motohiro
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Sprache:eng
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Zusammenfassung:The accumulation of a disease-specific isoform of prion protein (PrP ) and histopathological lesions, such as neuronal loss, are unevenly distributed in the brains of humans and animals affected with prion diseases. This distribution varies depending on the diseases and/or the combinations of prion strain and experimental animal. The brain region-dependent distribution of PrP and neuropathological lesions suggests a neuronal cell-type-dependent prion propagation and vulnerability to prion infection. However, the underlying mechanism is largely unknown. In this study, we provided evidence that the prion 22L strain propagates more efficiently in excitatory neurons than inhibitory neurons and that excitatory neurons in the thalamus are vulnerable to prion infection. PrP accumulation was less intense in the striatum, where GABAergic inhibitory neurons predominate, compared to the cerebral cortex and thalamus, where glutamatergic excitatory neurons are predominant, in mice intracerebrally or intraperitoneally inoculated with the 22L strain. PrP stains were observed along the needle track after stereotaxic injection into the striatum, whereas they were also observed away from the needle track in the thalamus. Consistent with inefficient prion propagation in the striatum, the 22L prion propagated more efficiently in glutamatergic neurons than GABAergic neurons in primary neuronal cultures. RNAscope hybridization revealed a decrease in - and -expressing neurons in the ventral posterolateral nuclei of the thalamus in 22L strain-infected mice, whereas no decrease in -expressing neurons was observed in the adjacent reticular nucleus, mainly composed of -expressing interneurons. The excitatory neuron-prone prion propagation and excitatory neuronal loss in 22L strain-infected mice shed light on the neuropathological mechanism of prion diseases.
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2024.1498142